One of the principal mechanisms by which cellular regulation is effected is through the transduction of extracellular signals across the membrane that in turn modulate biochemical pathways within the cell. Protein phosphorylation represents one course by which intracellular signals are propagated from molecule to molecule resulting finally in a cellular response. These signal transduction cascades are highly regulated and often overlapping as evidenced by the existence of many protein kinases and phosphatases as well as adapter and effector molecules.
It is currently believed that a number of disease states and/or disorders are a result of either aberrant expression or functional mutations in the molecular components of kinase cascades. Consequently, considerable attention has been devoted to the characterization of these proteins.
MP-1 (also known as MEK Partner 1) is a recently discovered adapter protein that participates in the extracellular signal-regulated kinase (ERK) cascade. This pathway has been shown to mediate the regulation of growth, differentiation and apoptosis (Elion, Science, 1998, 281, 1625-1626).
MP-1 was first isolated in the mouse and shown to selectively associate with MEK1 and ERK1 and enhance their activation through the B-Raf/MEK1/ERK1 pathway. When overexpressed MP-1 increased the number of MEK1-ERK1 complexes and the activation of downstream targets such as ELK-1 (Schaeffer et al., Science, 1998, 281, 1668-1671). These results support the notion that MP-1 acts as an adapter molecule which may link two or more MAP kinase signaling pathways.
Currently, there are no known therapeutic agents which effectively inhibit the synthesis of MP-1. Consequently, there remains a long felt need for additional agents capable of effectively inhibiting MP-1 function.
It is anticipated that antisense oligonucleotides against MP-1 may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the effective and specific modulation of MP-1 expression. The present invention provides compositions and methods for modulating MP-1 expression.